tbuckley/cabot-search huggingface dataset:
Abstract 14581: Massive Sinus of Valsalva Aneurysm With Rupture Into the Right Atrium
Authors: George Khludenev, Iniya Rajendran, Ramzi Ibrahim, Tushar Acharya, Kwan Seung S Lee, Michel Corban, Michael Insel, Michael D Seckeler, Franz Rischard, Saad Kubba
Journal: Circulation (2022)

Case Presentation: A 40-year-old male presented with decompensated heart failure and severe pulmonary hypertension (echo-predicted right ventricular systolic pressure 60 mmHg). Right heart catheterization revealed high output heart failure (cardiac index 7.3 L/min/m 2 ), left to right shunt (Qp:Qs 3.6:1), pulmonary hypertension (mean 38 mmHg), and normal pulmonary resistance (1.53 Wood units). Transesophageal echocardiogram revealed a large non-coronary sinus of Valsalva aneurysm with communication to the right atrium (Figure 1a and b). Percutaneous transcatheter closure of the aneurysm was deferred due to large size (3.3 x 4.3 cm), proximity to the right coronary artery, and risk of aneurysm rupture with catheter manipulation (Figure 1c). The patient underwent surgical aneurysm resection and aortic root replacement and recovered well. Discussion: Sinus of Valsalva aneurysms (SVAs) are rare pathologies characterized by expansion of the aortic root wall between the sinotubular junction and the aortic valve annulus and are often associated with connective tissue disorders. SVAs are often diagnosed incidentally on imaging but can present with symptoms if they rupture into nearby cardiac structures, such as an aorto-atrial fistula with left to right shunting, high output heart failure and hemodynamic compromise, as in this case. While transthoracic echocardiogram is the diagnostic modality of choice for most SVAs, multimodality imaging, catheterization, and advanced imaging may also be needed. Surgical repair remains the gold standard of therapy, however treatment with transcatheter device placement has also been successfully performed.
Abstract 14554: Novel Upstream Targets for Atrial Fibrillation
Authors: Padmini Sirish, Jun Yang, Esha Datta, Aditya Ballal, Uma N Srivatsa, Bob Kiaii, Leighton Izu, Bruce D Hammock, Nipavan Chiamvimonvat
Journal: Circulation (2022)

Introduction: Atrial fibrillation (AF) represents one of the most common arrhythmias seen clinically and is associated with a significant increase in morbidity and mortality, yet, current treatment paradigms have proven largely inadequate. One of the main contributors to the pathophysiology of AF is inflammation. Hence, reduction of inflammation associated atrial remodeling represents a novel therapeutic strategy for the treatment of AF. One of the most biologically important groups of oxylipins (oxygenated lipids) is the eicosanoids that are potent modulators of immune responses and are derived from arachidonic acid, linoleic acid among others, which are metabolized through three pathways including the cytochrome P450 (CYP) pathway. The CYP products are major anti-inflammatory metabolites with several cardioprotective effects. Hypothesis: We hypothesize that lipid metabolites may represent a new therapeutic target for AF Methods: In the cross-sectional study, human atrial appendage specimens and blood from informed and consented patients were obtained in accordance with the approved UC Davis IRB protocol. Metabolomic profiling for over 100 metabolites was assessed from the plasma of patients using LC-MS/MS. We used Functional Connectome, an extension of the singular value decomposition for matrices, to determine how the metabolites were functionally related to each other. The underlying mechanisms of AF were determined using an integrated approach with molecular biology, flow cytometry, and electrophysiology. Results: Metabolomic profiling shows a significant difference in several metabolites from the arachidonic and linoleic acid pathways in the cohort with AF compared to patients in NSR. There was a significant increase in oxidative stress, endoplasmic reticulum stress, inflammatory cytokines, nuclear translocation of NF-κB, and the activation of MAPK and TGF-b pathways from patients with AF compared to NSR cohort. Conclusions: The study provides important insights into the functional relatedness of the metabolites from the CYP pathway in patients with AF and reveals the prospect of arachidonic and linoleic acid metabolites being novel therapeutic targets in the treatment of AF.
Abstract 14641: Diastolic Dysfunction “In a Dish“- A Novel Organoid Model of Heart Failure With Preserved Ejection Fraction
Authors: Idan R Haiim, Caroline Bashai, Noam Kazma, Anastasia Nevo, Oren Caspi
Journal: Circulation (2022)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a major cause of mortality. No therapies have shown a survival benefit in HFpEF. A potential reason may be the lack of an in-vitro model for identifying novel therapeutic targets. Here, we aimed at generating a model of HFpEF using engineered cardiac organoids. Methods: Human cardiomyocytes generated from human-induced pluripotent stem cells were used to form 3D cardiac organoids. The organoids were exposed to conditions mimicking the comorbid conditions (Diabetes, hypertension, obesity, inflammation) leading to HFpEF: high glucose media with insulin deprivation; pro-fibrotic and hypertrophic stimuli such as Angiotensin II and Endothelin-1; free fatty acids, and pro-inflammatory factors ( e.g., IL-1 ). The passive stiffness, active contractile forces, and tau (relaxation constant) were evaluated using a force-transducer and a length controller. Structural and molecular phenotyping were conducted as well. Results: Exposure to HFpEF-inducing media resulted in single cells hypertrophy with an increase of average cell size (6670.87±1363.86 um^2) in comparison to control media (2840.56±520.70 um^2). The generated organoids exposed to HFpEF media developed a significant increase in passive force of 7.35±2.47 N/m vs. 2.04±0.85 N/m for control. Relaxation was prolonged in the HFpEF media and resulted in an increased ratio of 1.87±0.21 of relaxation constant, tau, in comparison to baseline and no modulation of tau in the control (1.08± 0.08 ). Structural and molecular evaluation showed characteristic HFpEF phenotype. Discussion: Cardiac organoids can recapitulate HFpEF phenotypes such as the increase in passive force, elongation of diastole, hypertrophy, and no change in the active force. An HFpEF in-vitro model may provide an unprecedented insight into the early pathogenetic mechanisms involved in HFpEF and may serve as a high-throughput platform for drug discovery.
Abstract 14753: Impact of Automation on Time Burden of Echocardiographic LVEF Measurements: A Systematic Review and Meta-Analysis
Authors: Mark Nolan, Thomas Marwick, Paaladinesh Thavendiranathan
Journal: Circulation (2022)

Introduction: Impact of time savings with the use of automated left ventricular volume measurements has not been systematically quantified. Hypothesis: Automated measurement of left ventricular volumes will lead to significant time savings. Methods: Electronic search of MEDLINE and EMBASE was performed. Inclusion criteria included 1) LVEF (either 2D or 3D) quantification using completely automated software, 2) comparator group of manual measurements and 3) stated mean and standard deviation of measurement time. Meta-analysis was performed with studies weighted by DerSimonian-Laird method and pooled using random-effects model. Results: 6 studies of automated 3D-LVEF measurement were identified with total of 697 pts. Time savings for 3D-LVEF automation was -371.0 seconds per study (95%CI -754.6 to +12.6 seconds, p = 0.058, Q (df=5) 2104.3, I2 99.9%), which was non-significant. HeartModel (Phillips) was used in 4 studies with 550 patients with non-significant time savings of -452.3 seconds (95%CI -1029.5 to +124.9 seconds, p=0.12, Q(df=3) 1954.1, I2 99.9%). 4D AutoLVQ (GE) was used in 1 study of 103 patients with significant time savings (142±30 sec vs. 226±114 sec, p&lt;0.001). A single study of 44 pts used eSieLVA(Siemens) with significant time savings (37 ± 8 sec vs 371 ± 116 sec, p&lt;0.001). For automated 2D-LVEF measurements, 6 studies were identified with total of 681 pts with total time savings with automation of -65.8 seconds, (95%CI -86.3 to -45.3 seconds, p &lt; 0.001, Q(df=5) 86.1, I 2 98.7%). AutoEF (GE) was used in 3 studies with total of 230 pts with time-savings of -49.6 seconds (95%CI -59.6 to -39.7, p&lt;0.0001, Q(df=2) 15.3, I2 88.2%). Auto EF (Siemens) was used in 2 studies, total 267 pts, with time savings of -75.2 seconds, (95%CI -118.3 to -32.1 sec, p=0.0006, Q(df=1) 24.7, I2 96.0%). A2DQ(Phillips) was used in 1 study of 184 pts (41 ± 5 sec vs. 98 ± 8 sec, p&lt;0.001). Subgroup analysis did not reveal significant difference in time savings between 2D-LVEF software (p=0.26). Conclusions: Significant time savings were observed for automated 2D-LVEF measurements with nonsignificant trend for automated 3D-LVEF measurements. Adoption of automated LVEF measurements may contribute to improved echocardiography lab efficiency.
Abstract 14462: Diversity of Cardiology Fellowship Candidates in the Era of Virtual Interviews
Authors: Celeste Witting, Santosh E Gummidipundi, Paul A Heidenreich, Josh Knowles, Celina M Yong
Journal: Circulation (2022)

Introduction: The goal of cardiovascular training programs is to increase recruitment of women and underrepresented in medicine (UIM) trainees. Due to the COVID-19 pandemic, virtual interviewing replaced in-person interviewing for cardiology fellowship applications in the United States. However, there is little data on the influence of these changes on fellowship candidate diversity. Methods: In a single-center retrospective study, we identified demographic changes in the profiles of trainees who interviewed for the Stanford University Cardiovascular Fellowship Program before and after the transition to virtual interviewing (2019 and 2020 vs 2021 and 2022 cycles). UIM applicants were defined as those who self-identified Black or Hispanic. Test of proportions and t-test were used for categorical and numeric variables respectively. Results: Over four years, 2250 trainees applied, 212 candidates interviewed, and 24 were accepted to the fellowship. Of those interviewed, 42.0% were women, 9.9% were Black, and 9.4% were Hispanic. The proportion of UIM trainees interviewed increased from 10.5% during the in-person years to 30.2% during the virtual years (p &lt; 0.001; Figure 1A). The increase among women was not statistically significant (40% in-person vs. 44% virtual, p = 0.58). The geographic distribution shifted over time to include lower representation from closer Western programs (40% in-person to 29% virtual) and higher representation from Northeast programs (35% in-person to 44% virtual; Figure 1B). The weighted mean distance of represented residency programs nominally increased from 1730 miles to 2067 miles away (p = 0.06). Conclusions: Virtual interviews were associated with a three-fold increase in UIM interviewed applicants for cardiology fellowship positions at a single center. Further research is warranted to assess the full impact of virtual interviews, as well as to understand and mitigate potential bias in the evolving selection process.
Abstract 15421: Mice Deficient in Endothelial Cell-Selective Adhesion Molecule Display Coronary Microvascular Rarefaction and Left Ventricle Diastolic Dysfunction
Authors: Vadym Buncha, Katie A Fopiano, Liwei Lang, Ricardo A Arriaga, Zsolt A Bagi
Journal: Circulation (2022)

Coronary microvascular dysfunction and chronic inflammation play a role in the development of left ventricular diastolic dysfunction (LVDD) in heart failure with preserved ejection fraction (HFpEF). Endothelial cell-selective adhesion molecule (ESAM) is part of the endothelial cell junction complex, which plays a role in the maintenance of cell barrier function, inflammatory cell transmigration and angiogenesis. Here, we examined the role of ESAM in affecting coronary microvascular density and left ventricle diastolic function by employing mice with genetic deletion of ESAM (ESAM -/- ). Using echocardiography, we found that ESAM -/- mice display LVDD, as indicated by a significantly (p&lt;0.05) reduced E/A ratio (E=early, A=late mitral inflow peak velocities), increased E/e’ ratio, isovolumic relaxation time and E wave deceleration time, with no change in the ejection fraction. Using an unbiased, automated tracing and 3D reconstruction of microvascular network revealed that ESAM -/- mice have a reduced coronary microvascular density, which was accompanied by myocardial accumulation of myeloperoxidase-positive neutrophils and elevated myocardial levels of inflammatory cytokines and chemokines. ESAM -/- mice exhibited a reduced endothelial sprout formation in the carotid artery, whereas in cultured endothelial cells siRNA-mediated ESAM knockdown impaired tube formation. Thus, ESAM deficiency in mice leads to coronary microvascular rarefaction, which likely via a myocardial hypoperfusion-related neutrophil accumulation and inflammatory mediator production impairs LV diastolic function.
Abstract 14807: Effect of Psychiatric Illnesses on the Stress Induced Cardiomyopathy Readmission
Authors: Dhrubajyoti Bandyopadhyay, aaqib malik, Akshay Goel, Rahul Gupta, Adrija Hajra, Wilbert S Aronow
Journal: Circulation (2022)

Introduction: Stress-induced cardiomyopathy (SIC) is a form of transient non-ischemic cardiomyopathy that is precipitated in the setting of acute emotional or physical stress. Postulated hypothesis implicated catecholaminergic excess and a role of the brain-heart axis behind its pathogenesis. The impact of different psychiatric illnesses on the outcomes of SIC is not clear. Method: We conducted a retrospective study using National Readmission Database (NRD) from 2011 to 2019 using ICD-10-CM (International Classification of Diseases, 10th Edition, Clinical Modification) and ICD-9-CM codes to identify the admissions with the discharge diagnosis of SIC and stratified them based on the presence of psychiatric illnesses. The primary outcome was six-month readmission and predictors of readmission. Result: We included a total of 98,721 admissions with a diagnosis of SIC. Among them, 12.9% had major depression, 1.8% had bipolar disorder, 17.6% had an anxiety disorder, and 0.6% had schizophrenia. Overall, patients with psychiatric illnesses were younger. Patients with psychiatric illnesses had a higher burden of comorbidities. Patients with schizophrenia had higher in-hospital mortality. Patients with psychiatric illnesses had a higher likelihood of getting readmitted within six months (p&lt;0.001). The significant independent positive predictors of readmission within 6 months were history of diabetes [odds ratio (OR):1.21, confidence interval (CI):1.16-1.26], heart failure (OR:1.31, CI:1.26-1.36), CKD/ESRD (OR: 1.44, CI:1.37-1.51), AF (OR: 1.25, CI:1.20-1.31), anemia (OR:1.24, CI: 1.15-1.34), peripheral arterial disease (OR: 1.25, CI:1.18-1.33), chronic obstructive pulmonary disease (OR: 1.35, CI:1.29-1.40), and prior stroke (OR: 1.10, CI: 1.02-1.18). Conclusion: We witnessed that psychiatric illnesses were associated with a higher likelihood of six-month readmission in patients with SIC.
Abstract 14733: Fluid Around a Small Heart- Cardiac Manifestation of Anorexia Nervosa
Authors: Ajay K Mishra, THRISHALA REDDY KASIREDDY, Deepti Kumar
Journal: Circulation (2022)

Background: Anorexia Nervosa (AN) is an eating disorder which is characterized by an abnormally low body weight (BMI&lt;18.5), a distorted perception of weight and an intense fear of gaining weight. It is prevalent in about 0.3 to 1% of the US population. Diverse cardiovascular complications are noted in these patients including decreased cardiac output, left ventricular mass and dimensions; pericardial effusion, bradycardia, hypotension and prolonged QT interval. We report a patient presenting with recurrent chest pain, and was diagnosed to have pericardial effusion secondary to AN. Case Presentation: A 27-year-old female with history of iron deficiency anemia, benign ethnic neutropenia, anorexia nervosa and borderline personality disorder, presented with insidious onset of atypical chest pain in the substernal region. Her BMI at presentation was 18.4, vital signs and systemic examination were normal. EKG showed a prolonged QT interval. She was noted to have normal blood cell counts, metabolic parameters and cardiac enzymes. A limited bedside echocardiography was normal except for the presence of mild pericardial effusion. She was treated with anti-inflammatory agents and discharged. A week later she presented with similar complaints. Management: Repeat cell counts were normal. Electrolytes revealed mild hypokalemia. Her CXR showed evidence of microcardia with a pulmonary artery diameter of 0.40. A repeat echocardiogram showed persistence of mild to moderate pericardial effusion. Etiological evaluation was negative for infections, autoimmune markers, and thyroid abnormalities. There was no evidence of ischemia and no rhythm abnormality. Her symptoms improved with analgesics and reassurance. Conclusion: Eating disorders like AN, have protean cardiovascular manifestations. Atypical chest pain in patients with AN is mostly idiopathic (38%) in the absence of risk factors. Silent pericardial effusion is found in about 22% to 71% of patients with AN. In these patients, factors like low BMI, rapid weight loss, low T3 levels, and IGF-1 levels correlate with pericardial effusion. Most patients show resolution of the effusion, normal cardiac dimensions and QT interval, after weight restoration without further intervention necessary.
Abstract 14557: Prognostic Role of Pathogenic Mutations in Brugada Syndrome: Results From Wide Gene Testing
Authors: Luigi Pannone, Antonio Bisignani, Randy Osei, Anais GAUTHEY, Antonio Sorgente, Pasquale Vergara, Cinzia Monaco, Domenico Della Rocca, Ingrid Overeinder, Gezim Bala, Alexandre Almorad, Erwin Ströker, Juan Sieira, Thomy de Ravel, Pedro BRUGADA, Mark La Meir, Gian Battista Chierchia, Sonia Van Dooren, Carlo de Asmundis
Journal: Circulation (2022)

Introduction: A pathogenic/likely pathogenic (P/LP) mutation can be found in 20-25% of patients with Brugada syndrome (BrS) and a P/LP mutation in SCN5A is associated with a worse prognosis. However, the prognosis of non SCN5A genes mutations is unclear. Methods: All BrS patients, were prospectively enrolled in the UZB registry between 1992 and 2022. Inclusion criteria for this study were: 1) BrS diagnosis; 2) Genetic analysis performed with a wide gene panel; 3) Classification of variants following ACMG guidelines. Patients with a P/LP variant in SCN5A were defined as (P+/SCN5A+); patients with a P/LP variant in a gene different from SCN5A were defined as (P+/SCN5A-). All other patients were classified as (P-). Results: A total of 452 BrS patients were analyzed. Any P/LP mutation was found in 108 (23.9%) patients, 94 (20.8%) patients P+/SCN5A+ and 14 (3.1%) patients P+/SCN5A-. Compared with P- patients, P+ patients were younger, more frequently had a spontaneous BrS type I ECG, sinus node dysfunction, aborted sudden cardiac death history and longer PQ interval, Table 1. After a mean follow-up of 116.7 months, 47 patients (10.4%) experienced a ventricular arrhythmia (VA). At survival analysis, P- patients had higher VA free survival, compared with P+/SCN5A+ (93% vs 81.9%, p=0.023) and with P+/SCN5A- (93% vs 57.1%, p&lt;0.001). Among P+ patients, P+/SCN5A+ patients had higher VA free survival compared with P+/SCN5A- (81.9% vs 57.1%, p=0.023), Figure 2. At Cox multivariate analysis, P+ was an independent predictor of VA occurrence (HR= 2.23, CI 95% 1.10-4.58, p=0.027). Conclusions: In a large BrS cohort, the diagnostic yield for P/LP mutations is 23.9%. P+ is an independent predictor of VA.
Abstract 14679: Electrocardiogram Findings From Athletic Adaptation and COVID-19 Infection in Collegiate Football Players
Authors: McKenna C Noe, Erika Parisi, Darryl Conway, Lenny Navitskis, Sami Rifat, Eugene H Chung
Journal: Circulation (2022)

Introduction: Improved criteria have enhanced the sensitivity and specificity of the 12-lead ECG to identify underlying cardiovascular conditions predisposing to sudden cardiac death or morbidity. However, the impacts of chronic high-intensity exercise and especially ethnicity on changes in longitudinal ECG remain unknown. Furthermore, given the ongoing pandemic, we must consider how COVID19 infection may impact ECG findings. We analyzed collegiate student athlete ECGs over time to determine whether longitudinal training, race, and post-COVID19 status impact the ECG findings with the goal of informing future interpretation criteria. Methods: We included twenty-two NCAA Division I football players from January 2018 to January 2021. Ten athletes contracted COVID19 during this period. We compared pre-season ECGs prior to the first and third years of athletic participation as well as any within 34 days after confirmed COVID19 infection. Heart rate, QRS duration, QT interval, and any International Criteria findings were identified. The ECGs acquired prior to the athlete’s first-year of participation served as the baseline for comparison for the third-year and post-COVID19 ECG. T-tests and two-sample z-tests were used as appropriate for statistical analysis. Results: Compared to matched first-year baseline, the QRS duration of post-COVID19 ECGs was significantly longer (102 ± 26 ms vs 100 ± 31 ms, p = 0.01, 95% CI 0.62-3.77), which was not seen when compared to matched third-year ECGs. There were no other significant differences between white and black athletes, or those of third-year ECGs compared to the matched first-year baseline. Conclusions: In this small cohort of 22 athletes, there was no significant change in heart rate, QRS duration, QT interval, or International Criteria classifications, including early repolarization and voltage, between first- and third-year ECGs of white and black athletes. Although the post-COVID19 QRS duration was significantly increased compared to first-year ECGs, the range was still within normal; there was no increase with respect to third-year ECGs. Further analysis of a larger sampling of athletes of different sexes and sports that also considers the impact of training on the post-COVID ECG is ongoing.